Acne vulgaris is a skin disease of youths involving comedos, papulae, pustules, etc. appearing on the face, the center of the chest, the upper part of the back, etc. Main causes of acne vulgaris include (1) hypersteatosis, (2) stricture of hair-follicles, and (3) proliferation of Propionibacterium acnes, one of Gram positive anaerobic bacteria, in the pilosebaceous gland.
Conventional treatments of acne vulgaris are focused on removal of the above-described three main causes. For example, female hormones are applied to suppression of hypersteatosis; keratolytic substances, e.g., salicylic acid, resorcin, etc. are applied to elimination of stricture of hair-follicles; and bactericidal disinfectants, e.g., Chlorohexidine gluconate, are applied to inhibition the proliferation of the bacterium.
However, conventional bactericidal disinfectants essentially have side effects of causing erythema or exfoliation, thus toughening and irritating skin. It has therefore been difficult to obtain the full effect of such bactericidals due to their limited allowable dose.
In recent years, various naturally occurring substances or synthetic compounds which are antibacterial components safe to the skin have been proposed in the treatment of acne vulgaris. Examples of so-far proposed antibacterial components of natural origin include Ferruginol (see JP-A-1-311018, the term "JP-A" as used herein means an "unexamined published Japanese patent application"), Totarol (see JP-A-1-311019), Sempervirol (see JP-A-1-311020), tetrahydroabietic acid and its esters (see JP-A-2-188513), and anacardic acid (see JP-A-4-36238). 1-Hydroxy-2-pyridone (see U.S. Pat. No. 4,762,847 (1988)) may be mentioned as an example of the synthetic antibacterial component to be used in the treatment of acne vulgaris.
However, since the naturally occurring antibacterial substances are scarce in nature, and the synthetic compounds are not easy to synthesize, both are not easily available and therefore unsatisfactory as an active ingredient for the treatment of acne vulgaris.
1-Pentadecanol, which is the active ingredient of the topical composition for treating acne vulgaris according to the present invention, is a straight chain primary alcohol (1-alkanol) having 15 carbon atoms. In general, 1-alkanols are known to possess antibacterial activity, and it was reported that the effectiveness of 1-alkanols considerably varies depending on the object bacteria (see Nobuyuki Kato, et al., J. Antibact. Antifung. Agents, vol. 8, No. 8, pp 1-7 (1980)).
According to this report, a 1-alkanol having 12 or 13 carbon atoms is the most effective on Staphylococcus aureaus, one of Gram positive bacteria, among 1-alkanols having 10 to 16 carbon atoms. A 1-Alkanol with 15 carbon atoms has a considerably lesser effect, and that with 16 carbon atoms produces no substantial effect. It is also known that a 1-alkanol with 11 carbon atoms is the most effective on Aspergillus niger, which belongs to fungi, and that this antifungal activity is almost lost with an increase of carbon atom number by only one. Further, it was reported that 1-alkanols having 14 to 15 carbon atoms are the most effective against Streptococcus mutans, and that one with 16 carbon atoms has substantially no effect (see M. Hattori, et al., Chem. Pharm. Bull., Vol. 35, No. 8, pp 3507-3510 (1987)).
All of the above-mentioned 1-alkanols are on the market and easily available. Some of these 1-alkanols have been confirmed to be safe when applied to the skin and now widely employed as cosmetic bases. For example, lauryl alcohol having 12 carbon atoms (i.e., 1-dodecanol), cetanol having 16 carbon atoms (i.e., 1-hexadecanol), and stearyl alcohol having 18 carbon atoms (i.e., 1-octadecanol) are specified in Standards of Cosmetic Materials edited by Nippon Koteisho Kyokai.
Known formulations of acne vulgaris treating compositions for external use containing a 1-alkanol as a base include a composition comprising benzoyl peroxide as an active ingredient having incorporated therein a primary alcohol having from 6 to 14 carbon atoms for enhancing penetration of the active ingredient into the skin, a diol, and other vehicles (see JP-A-55-120514 corresponding to EP-A-13459), a composition comprising a specific antibiotic, a penetrability improving agent, such as lauryl alcohol, and vehicles, such as ethanol (see JP-A-56-99416 corresponding to U.S. Pat. No. 4,299,826 and EP-A-27286), a composition comprising a specific compound having anti-androkinin activity, an alcohol, such as an aliphatic alcohol having from 1 to 18 carbon atoms, as a solvent and a humectant (see JP-A-61-36219 corresponding to U.S. Pat. No. 4,657,901 and EP-A-138029), a composition excellent in percutaneous absorption and bioavailability comprising an active ingredient, such as benzoyl peroxide, from 20 to 40% by weight of an aliphatic alcohol having from 12 to 22 carbon atoms, volatile silicone as another base, and other additives such as a preservative (see JP-W-61-501091 (the term "JP-W" as used herein means an "unexamined published international patent application") corresponding to U.S. Pat. No. 4,678,663 and EP 172228), a composition containing a lower alcohol, e.g., ethanol, as a compatibilizer between an oily substance and a volatile oil (see JP-A-63-27425), other compositions containing a lower alcohol, e.g., ethanol (JP-A-48-4646 corresponding to U.S. Pat. No. 3,806,593 and GB Patent 1388836 and JP-A-53-94027 corresponding to GB Patent 1551637), and a composition comprising an active agent for killing acne bacteria, a fatty acid and an aliphatic alcohol with the expectation of synergistic effects (see JP-A-2-96522 corresponding to EP Patent 331489).
In all of the above-cited publications, 1-alkanols are described as a base for serving as a solvent, a humectant, an accelerator of percutaneous absorption, and the like in compositions for treating acne vulgaris containing other compounds as active ingredients, with no mention of any effect of the 1-alkanols per se on acne vulgaris.
Formulations containing a 1-alkanol as an active ingredient for treating acne vulgaris are also known. For example, JP-A-60-152415 discloses a composition containing ethanol as a main ingredient exhibiting antibacterial activity on Propionibacterium acnes, and U.S. Pat. No. 4,052,515 proposes a method for treating acne vulgaris comprising applying a combination of a higher alcohol having from 6 to 12 carbon atoms and a lower alcohol to the affected skin and describes the antibacterial activity of the combination against Corynebacterium acne. U.S. Pat. No. 4,657,935 teaches gargling with a mixture of water and an alcohol for treatment of acne vulgaris, but the publication does not specify the composition and the effect of the alcohol used.
As aforementioned, various reports on 1-alkanols have been made to date. However, the present inventors find no report on use of 1-pentadecanol as an active ingredient for treating acne vulgaris, still less the antibacterial activity of 1-pentadecanol on Propionibacterium acnes.
Use of 1-alkanols containing from 1 up to 22 carbon atoms as a base of acne vulgaris treating agents for external application has already been disclosed, and 1-pentadecanol is included among these alkanols. However, 1-pentadecanol is not so common as a base, and there is found no specific formulation example using 1-pentadecanol.